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An Immune System Marker For Therapy-Resistant Prostate Cancer

In RApidCaP, a mouse model of human metastatic prostate
cancer that they developed, researchers have identified an
immune system marker that may help to distinguish patients
who will and will not respond to hormone therapy. That marker
is IL-6, an immune system component whose presence is
indicated in brown patches in the image at left, in a section
of lung tissue (blue) colonized by prostate cancer cells. The
middle image of the same section of lung tissue indicates
activation of STAT3, a protein that is the downstream target
of IL-6 signaling. The image at right of the same tissue section
demonstrates the presence of PCNA in the invading prostate
cells, a marker of metastasis.
(Credit: Courtesy of Trotman Lab/ CSHL)

You are a patient who has just been treated for a serious illness but neither you nor your doctor knows how likely it is that you - in comparison with other patients - will actually be helped by the treatment. This is often the situation with prostate cancer, one of the deadliest and most highly prevalent cancers. While hormone therapy can help, patient responses vary widely, and it's still unclear why some types of prostate cancer seem to be resistant to the therapy.

In work published in the journal Cancer Discovery, researchers show how signaling by an immune system component called interleukin-6 (IL-6) appears to play an important role in driving particularly aggressive and therapy-resistant prostate cancer. They also suggest that IL-6 could be a marker for when the disease switches to a more dangerous state that is ultimately hormone therapy-resistant.

The researchers also looked for cellular signals that led to metastasis and hormone therapy resistance in a genetically engineered mouse model for metastatic prostate cancer. They found that the combined loss of two genes, PTEN and p53 - closely associated with prostate cancer metastasis - led to the secretion of IL-6. Signaling by IL-6 was then responsible for activating a powerful cancer gene called MYC, which drives cell proliferation and disease progression.

The results could have important implications for prostate cancer patients. The variability in response to hormone therapy is amazing. For one person this therapy might be great, might reduce disease burden dramatically for many years, and be an extreme benefit. For others there's almost no response, and it's still not clear to clinicians who is who. Translating the IL-6 discovery into the clinics could help identify patients into good responders and bad responders. The involvement of the MYC pathway also suggests that it could potentially serve as a target of drugs against prostate cancer.